A Phase II Clinical Trial of Chiglitazar for NASH

NASH Clinical Trial

Official title:

A Multi-Center, Randomised, Double-blind, Placebo Controlled Phase II Clinical Study of Chiglitazar in Patients With Nonalcoholic Steatohepatitis Accompanied by Elevated Triglycerides and Insulin Resistance

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05193916
• Other study ID #: CGZ203
• Secondary ID: CINAR
• Status: Recruiting
• Phase: Phase 2
• Start date: March 21, 2022
• Est. completion date: February 2024

Study information

• Verified date: August 2023
• Source: Chipscreen Biosciences, Ltd.
• Contact: Hong You, Phd
• Phone: 86-10-63139019
• Email: youhong30[@]sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study is to evaluate the efficacy and safety of chiglitazar monotherapy in patients with non-clcoholic steatohepatitis (NASH).

Description:

The study is a non-invasive exploratory phase II trial in patients who were clinically diagnosed as non-alcoholic steatohepatitis (NASH) with liver fibrosis accompanied by elevated triglycerides (TG) and insulin resistance. The efficacy and safety of chiglitazar tablets 48mg and 64mg will be compared with placebo in the 18-week-treament.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: February 2024
• Est. primary completion date: February 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Before any evaluation, an informed consent form voluntarily signed by the patient must be obtained;

2. 18 -75 years old (at the time of screening visit V1), male or female;

3. MRI-PDFF = 8% ;

4. Liver stiffness value ( LSM ) 7.0-11.0kPa ;

5. Triglyceride ( TG ) =1.7mmol/L and =5.6 mmol/L;

6. HOMA-IR = 2.5 ;

7. Serum Alanine aminotransferease (ALT) = the upper limit of normal during screening.

Exclusion Criteria:

1. Type 1 diabetes;

2. Any of the following for type 2 diabetes:

• HbA1c = 8.5% during screening
• At the time of screening, = 2 oral hypoglycemic drugs combinations
• Receiving any of the following medications at screening: Thiazolidinediones (TZD) drugs, fibrates, glucagon-like peptide-1 (GLP-1) receptor agonists, insulin

3. Existing other liver diseases or history of liver diseases

4. History of transient ischemic attack or cerebrovascular accident;

5. History of myocardial infarction, or coronary angioplasty or coronary artery bypass surgery, unstable angina, heart failure (New York Heart Association NYHA grade III / IV ), or ECG signs of left ventricular hypertrophy, or serious arrhythmias ;

6. During screening, blood pressure = 160/100 mmHg ;

7. Previous or planned ( during the study period) bariatric surgery;

8. Liver transplantation history or planned liver transplantation;

9. Liver biopsy show liver cirrhosis or clinically diagnosed as cirrhosis;

10. Weight loss of more than 5% in 6 months before screening;

11. History of edema of lower limbs or whole body;

12. diagnosed as osteoporosis or any other known bone disease;

13. Donated blood or lost blood >400 ml within 8 weeks before the first medication;

14. With MRI scan contraindications;

15. In the past 5 years, there was a history of malignant tumors of any organ system;

16. Human immunodeficiency virus ( HIV ) test is positive;

17. Heavy drinking of alcohol for more than 3 months in a year;

18. Heavy smoking >30 per day within 1 year;

19. History of drug abuse in 12 months;

20. Drugs cumulatively for more than 1 month in the previous 3 months before screening, such as obeticholic acid ( OCA ), berberine;

21. Drugs that may cause liver damage for more than 2 weeks within 1 year before screening;

22. Patients received the following medications unless they have received a stable dose for at least 1 month before screening :Beta-blockers, thiazide diuretics, statins, niacin, ezetimibe, thyroid hormone;

23. The calculated eGFR < 60 mL/(min*1.73m^2 );

24. There is clinical evidence of liver decompensation or severe liver damage;

25. Low density lipoprotein cholesterol (LDL-C) = 3.4 mmol/L during screening ;

26. Platelet < 100×10^9 /L ;

27. Patient participating in other clinical trials of drugs or medical devices within 3 months prior to screening ;

28. Pregnant or breastfeeding women.

Related Conditions & MeSH terms

• NASH

Intervention

Drug:
• chiglitazar sodium tablets
the drugs will be given orally once a day
• Placebo
no active drug contained

Locations

Country	Name	City	State
China	Beijing Friendship Hospital, Capital Medical University	Beijing	Beijing
China	Beijing Youan Hospital, Capital Medical University	Beijing	Beijing
China	Peking University People's Hospital	Beijing	Beijing
China	The First Hospital of Jilin University	Ch'ang-ch'un	Jilin
China	Foshan First People's Hospital	Foshan	Guangdong
China	The First Affiliated Hospital of Sun Yat-sen University	Guangzhou	Guangdong
China	Affiliated Hospital of Hangzhou Normal University	Hangzhou	Zhejiang
China	First Affiliated Hospital of Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	The First Affiliated Hospital of Anhui Medical University	Hefei	Jiangsu
China	The First Hospital of Lanzhou University	Lanzhou	Gansu
China	Nanjing Second Hospital	Nanjing	Jiangsu
China	Shanghai Tongren Hospital	Shanghai	Shanghai
China	The Ninth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai
China	The First Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shaanxi
China	Henan Provincial People's Hospital	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Chipscreen Biosciences, Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage change from baseline to week 18 in liver fat content as measured by MRI using the proton density fat fraction (MRI-PDFF)	center reading for the primary endpoint	18 weeks
Secondary	the change in liver fat content from baseline as shown by MRI-PDFF after 18 weeks treatment	Absolute decrease in liver fat content Proportion of patients with Liver fat content absolute decrease =5% Proportion of patients with Liver fat content relative decrease =30% proportion	18 weeks
Secondary	ALT changes from baseline	changes from baseline in liver enzymes	6,12,18 weeks
Secondary	FIB-4 changes from baseline	changes from baseline in Fibrosis 4 Score	6,12,18 weeks
Secondary	insulin resistance changes	Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)	6,12,18 weeks
Secondary	Changes from baseline in TG	blood sample	6,12,18 weeks
Secondary	change from baseline in Liver stiffness measurement (LSM) with Fibroscan	to evlaute the severity of liver fibrosis	6,12,18 weeks
Secondary	change from baseline in Cytokeratin18 (CK-18)	to evaluate the severity of liver damage	6,12,18 weeks
Secondary	Maximum Plasma Concentration [Cmax] of chiglitazar after 1 dose, 6 weeks and 12 weeks of treatment	population PK	0, 6,12 weeks
Secondary	The area under the plasma drug concentration-time curve [AUC] of chiglitazar after 1 dose, 6 weeks and 12 weeks of treatment	population PK	0, 6,12 weeks